Elevated insulin levels in Pima Indian adults compared to weight-matched Caucasian controls suggest that cellular changes external to the pancreas may be important in the pathogenesis of diabetes mellitus. The aim of this project is to study several aspects of insulin function in cells obtained from normal and diabetic Pima Indians, in order to determine if diabetes mellitus is expressed in genetic differences at the cellular level. Fibroblast cultures have been established from normal and diabetic Pima Indians. Parameters of cell growth are being compared in the normal and diabetic cells, and insulin binding is being studied. In addition, cellular metabolism and transport functions are being studied in the presence and absence of insulin, in order to further investigate cell insulin action and to determine if cellular abnormalities in insulin response occur in individuals with diabetes.